The main objective of these studies is to learn more about the mechanisms by which known bladder carcinogens induce urinary bladder cancer in experimental animals. The model system has been selected for study in this project is the induction of bladder cancer in rats with N-butyl-N-(4-hydroxybutyl)nitrosamine (BHBN) and its principal urinary metabolite, N-butyl-N-(3-carboxypropyl) nitrosamine (BCPN). The urinary bladder is the only organ in the rat in which cancer is induced by the administration of BHBN or BCPN, and the incidence of bladder cancer in exposed rats is 100%. Greater than 90% of these bladder cancers are transitional cell carcinoma. The research proposed in this application is directed towards learning what metabolite of BHBN or BCPN is involved in the induction of bladder cancer, i.e., how are these nitrosamines metabolically activated? The hypothesis being tested is that a stable precursor of an activated metabolite derived from BCPN is formed in the liver and is excreted in urine, where it undergoes hydrolysis (either intravesically or intracellularly after absorption) with the liberation of an activated metabolite. At the present time, we do not believe that BCPN itself is metabolically activated directly by rat bladder epithelial cells.